The goals of the project are to characterize the pathogenesis, natural history and therapy of herpes simplex varus and varicella-zoster virus infection. Our clinical emphasis has been on genital herpes in normal and immune-impaired patients. Analysis of 8 years of suppressive acyclovir therapy in patients with frequently recurring herpes have shown the drug to remain effective, to be well-tolerated, and to not induce drug resistance. We continue to study the ability of ultraviolet light and other physical and chemical agents to induce recurrent herpes simplex infections in humans. In a placebo-controlled trial, topical sunblockers were found to significantly prevent uv induced reactivation of HSV-2 infection. A placebo-controlled trial in patients with frequent, spontaneously recurring oral herpes was completed, showing that acyclovir significantly reduces rates of outbreaks. Also during this past year we conducted a pilot study of new nucleoside analogs, FIAC and FIAU, for treatment of CMV infections in AIDS patients. Preliminary findings showed no effect on CMV at tolerable doses, but a marked suppression of Hepatitis B virus infection was achieved with FIAU, a finding which will be pursued vigorously. The major thrust of our laboratory effort in this project has been the analysis of HSV latency in human ganglia. During the past year we cloned and sequenced the latency-associated gene of HSV-2, identified its promoter, characterized the kinetics of its transcription, and analyzed its homology to the corresponding HSV-1 gene. We have begun experiments to determine whether this region of the genome accounts for differences in the rate of recurrences between HSV-1 and 2 in humans.